Bacterial translocation is defined as the passage of viable bacteria from the gastrointestinal (GI) tract through the GI mucosa to other organs such as the mesenteric lymph nodes, etc. The PI has demonstrated that certain indigenous bacteria readily translocate from the GI tract to these other organs in gnotobiotic mice colonized with these organisms but do not translocate from the GI tract in specific pathogen-free (SPF) mice. Thus, gnotobiotic and SPF mouse models can be manipulated to elucidate the mechanisms operating to confine indigenous bacteria to the GI tract. One mechanism that may inhibit translocation of certain indigenous bacteria is antagonism among the various bacteria in the GI tract. It will be determined if the reduction in population levels in the GI tract of indigenous E. coli by an antagonistic flora will be followed by an inhibition of translocation of E. coli. SPF mice also will be treated with nonabsorbable antibiotics to remove antagonistic bacteria thereby promoting translocation by allowing certain bacteria to increase in population levels in the GI tract. Bacterial translocation from the GI tract also may be inhibited by the host's immune system. SPF and gnotobiotic mice will be treated with immunosuppressive drugs to promote bacterial translocation. Athymic (nu/nu) and heterozygous (nu/+) mice will be compared to determine the role of the thymus in inhibiting bacterial translocation. The route of translocating bacteria from the GI tract will be followed by light, flourescence, and electron microscopy. Finally, phagocytic cells from gnotobiotic and SPF mice will be studied to determine their phagocytic and microbiocidal activities on translocating and nontranslocating bacteria indigenous to the GI tract.